Prediction of ARrhythmic Events With Positron Emission Tomography

Currently available electrophysiological approaches are limited in their ability to identify
the majority of patients with CAD and LV dysfunction that succumb to sudden cardiac death
(SCD). Half of the patients developing SCD are not inducible at electrophysiological testing
underscoring the need for new ways to identify substrates leading to arrhythmic death.
Viable chronically dysfunctional with reduced resting flow, or hibernating myocardium, not
amenable to revascularization appears to be a major risk factor for subsequent cardiac death
and is present in up to 60% of patients with ischemic cardiomyopathy. Cause specific
mortality data is limited but appears to be arrhythmic rather than from fatal myocardial
infarction or progressive heart failure. Revascularization improves survival but most
patients with hibernating myocardium are managed medically due to prohibitive procedural
risks or technical limitations. Basic studies in swine with hibernating myocardium
demonstrate SCD arising from VT/VF in the absence of myocardial scar or heart failure. The
central hypothesis of this proposal is that the presence of hibernating myocardium as
opposed to scar identifies a large subset of patients with ischemic cardiomyopathy that are
at high risk for SCD. We further hypothesize that this risk is related to inhomogeneity in
sympathetic innervation arising from chronic repetitive ischemia. PAREPET is a prospective
observational study that will enroll patients with coronary disease, Class I-III heart
failure and an ejection fraction ≤35%. Using positron emission tomography (PET), the
frequency and amount of hibernating myocardium will be quantified in patients that are not
candidates for coronary revascularization. Three Specific Aims are proposed. Aim 1 will
determine whether imaging the mismatch between viability (preserved 18F-2-deoxyglucose) and
reduced resting flow (13NH3) can predict an increased risk of SCD (or ICD discharge for
VT/VF as a surrogate end-point) in hibernating myocardium. Aim 2 will image norepinephrine
uptake using 11C-hydroxyephedrine to determine whether inhomogeneity in myocardial
sympathetic innervation predicts SCD risk better than viability testing. Aim 3 will identify
whether the substrate identified by PET is stable after an aborted SCD event by evaluating
temporal changes in function, viability and sympathetic innervation in patients with an ICD.
Our long-term objective is to develop better approaches to identify patients with CAD who
are most likely to benefit from primary prevention of SCD with placement an ICD.

Inclusion Criteria:

- LV EF ≤35% (by nuclear imaging, cardiac catheterization or echocardiography)

- Coronary artery disease documented by cardiac catheterization, a history of definite
myocardial infarction, or reversible ischemia on nuclear imaging

- New York State Heart Association functional Class I-III heart failure

- Not a candidate for surgical or percutaneous coronary revascularization at the time
of enrollment

Exclusion Criteria:

- History of resuscitated sudden cardiac death, sustained ventricular tachycardia,
appropriate implantable cardiac defibrillator (ICD) discharge, or unexplained syncope

- Myocardial infarction within 30 days

- Coronary artery bypass grafting within 1 year

- Percutaneous intervention within 3 months

- Claustrophobia or physical limitation that would preclude PET scanning

- Pregnancy

- Tricyclic antidepressant drug therapy

- Comorbidities that would be expected to result in noncardiac death within 2 years

- Inability to provide informed consent